Publisher Health

Osteoarthritis is a degenerative joint disease caused by the breakdown of cartilage that afflicts more than 35 million adults in the U.S. The exact mechanism of cartilage breakdown in osteoarthritis is unknown, but damage from mechanical stress with insufficient self-repair is believed to be the main culprit.
The composition of synovial fluid, or joint lubricant, changes significantly in osteoarthritis: The concentration and molecular weight of hyaluronic acid tends to decrease and is commonly used to diagnose the disease.
In Biointerphases, an AVS journal published by AIP Publishing, an international group of researchers explored the disease-driven breakdown of hyaluronan and the mechanistic implications of these changes on the lubrication and subsequent wear of joints.
“One of the most important properties of the synovial fluid is its viscosity,” said co-author Rosa Maria Espinosa-Marzal of the University of Illinois Urbana-Champaign. “Viscosity is a measure of the internal frictional force between adjacent layers of a fluid in relative motion, or, more simply, a fluid’s resistance to flow. Large, high molecular weight polymers such as hyaluronic acid play a significant role in maintaining a high viscosity of the synovial fluid, which helps maintain a fluid film and reduces friction between articulating surfaces during motion.”
Through analysis with neutron and light scattering (studies carried out by Changwoo Do and Tooba Shoaib at Oak Ridge National Laboratory), the team determined that the structure of the lipid-hyaluronic-acid complexes in the bulk solution is a function of concentration and its molecular weight.
Researchers at the University of Illinois Urbana-Champaign, Kangdi Sun and Espinosa-Marzal, in collaboration with Mark Rutland, from KTH Royal Institute of Technology, found the hyaluronic acid’s concentration and molecular weight both play a role in how the lubricant reacts with different surfaces.
“Our results show low molecular weight hyaluronic acid, which mimics osteoarthritis-diseased joints, hinders the adsorption of the hyaluronic-acid-lipid complex,” said Espinosa-Marzal. “The lack of the formation of an amorphous film on the surface may reflect a consequence of osteoarthritis, since this film should help reduce friction and wear.”
Their hypothesis is that this film’s absence may increase wear of the cartilage surface. In contrast, high molecular weight hyaluronic-acid-lipid complexes form an amorphous film, which presumably helps maintain the mechanical integrity and longevity of efficient lubrication in healthy cartilage.
Studies on hyaluronic acid itself and hyaluronic-acid-lipid complexes “do not entirely support hyaluronic acid’s role in providing high lubricity to the cartilage’s articular surface, which is still a bit controversial,” Espinosa-Marzal said. “Our results indicate that for low molecular weight hyaluronic acid, this is likely the case.”
By exploring the complex interplay between phospholipid and hyaluronic acid self-assembly, and the role of molecular weight on surface affinity, “our study illuminates a mechanism whereby the ‘vicious circle’ of osteoarthritis can be explained,” said Rutland.

Among Indigenous, rural non-industrial populations inhabiting the tropical forests of lowland Bolivia, researchers report, there appears to be an optimal balance between levels of food consumption and exercise that maximizes healthy brain aging and reduces the risk of disease.
“We hypothesize that energy gain from food intake was positively associated with late life brain health in the physically active, food-limited world of our ancestors, but that obesity and other manifestations of a Western lifestyle now lead to greater cognitive aging and dementia in middle and older ages,” said UC Santa Barbara professor of anthropology Michael Gurven, a senior co-author on a study that published in the Proceedings of the National Academy of Sciences.
For this paper, the researchers collaborated with the Tsimané and Mosetén tribes, two Indigenous populations that live along tributaries of the Amazon River that flow through lowland Bolivia. In comparison to urban post-industrialized populations, these groups have less reliable access to food and have to exert a lot of effort to get it. They also have less access to modern health care. Meanwhile, people in wealthy countries have largely grown accustomed to eating more and exercising less — habits that are associated with decreased brain volumes and faster cognitive decline.
“We set out to compare rates of brain aging between U.S. and European populations, and two Indigenous Bolivian populations: the Tsimané, who have very low rates of heart disease and minimal dementia, and the Mosetén, who are culturally similar to the Tsimané but whose lifestyle has shifted away from subsistence,” said Gurven, who co-directs the Tsimané Health and Life History Project, a two-decade NIH-funded longitudinal study of health and aging.
The researchers enrolled 1,165 Tsimané and Mosetén adults, aged 40-94 years, and provided them transportation from their remote villages to the closest hospital with a CT scanner. They then used methods developed by study co-author Andrei Irimia, an assistant professor in the USC Leonard Davis School of Gerontology, to accurately measure brain volume from the CT scans. They also measured the participants’ body mass index, blood pressure, total blood cholesterol and other biomarkers of cardiometabolic health.
“We found the fastest brain aging in the U.S. and European cohorts,” Gurven said. “It was slowest in Tsimané and intermediate in Mosetén.” Rates of brain atrophy, or brain shrinking, are correlated with cognitive decline and risks of neurodegenerative diseases such as dementia and Alzheimer’s. In addition to less brain atrophy, the researchers found improved cardiovascular health in the Indigenous groups compared to industrialized populations in the U.S. and Europe.
The environment of limited food availability plays a role in the brain and cardiovascular fitness of nonindustrial societies, according to Irimia, in that “humans historically spent a lot of time exercising out of necessity to find food and their brain aging profiles reflected this lifestyle.”
Studying the Mosetén population illuminated key findings: as a “sister” population to the Tsimané, they share similar languages, ancestral history and agrarian lifestyle. However, the Mosetén have more exposure to modern technology, medicine, infrastructure and education. Based on the researchers’ results, according to Gurven, “the Mosetén’s lifestyle is more vulnerable to the chronic diseases of aging than among the Tsimane, but less so than in post-industrialized countries.”
Among the Tsimané, BMI, adiposity and higher levels of “bad” cholesterol were associated with bigger brain volumes for age. This, however, may be due to individuals being more muscular, on average, than individuals in industrialized countries who have comparable BMIs. Only at the highest levels of BMI, adiposity and cholesterol — closer to the levels more typically observed in the U.S. — was brain volume compromised.
“Our analyses suggest that ‘too much of a good thing,’ or what we call the ’embarrassment of riches,’ seems to be what’s going on,” Gurven explained. “Greater adiposity, blood cholesterol and other indicators of nutrient intake increase with brain volume, but only up to a point — a ‘sweet spot.’ Not too little and not too much. Beyond the sweet spot, higher levels of adiposity and cholesterol are associated with a smaller brain volume — faster brain aging. That’s consistent with our current environment being mismatched to our evolved biology.”
Co-author Hillard Kaplan, an anthropologist at Chapman University and a co-director of the Tsimané Health and Life History Project, agrees. “During our evolutionary past, more food and less calories spent in getting it resulted in improved health, well-being and ultimately higher reproductive success,” he said. “This evolutionary history selected for psychological and physiological traits that made us desire extra food and less physical work, and with industrialization, those traits led us to overshoot the mark.”
According to Gurven, the study implications carry a hint of optimism. “The same active lifestyle that leads to a healthy heart seems to also lead to a healthy brain, and well into your 70s,” he said. “If people like the Tsimané and Mosetén have found a manageable life-long balance to stave off dementia, then there’s hope for the rest of us.”

Every year, norovirus causes hundreds of millions of cases of food poisoning — and the deaths of at least 50,000 children — yet there exists no real way to control it. The virus has proven exceptionally difficult to study in the lab, and scientists have struggled to develop effective vaccines and drugs.
A new study at Washington University School of Medicine in St. Louis describes a creative way to make a vaccine against norovirus by piggybacking on the highly effective vaccines for rotavirus, an unrelated virus that also causes diarrhea.
The researchers created an experimental rotavirus-norovirus combo vaccine by adding a key protein from norovirus to a harmless strain of rotavirus. Mice that received the experimental vaccine produced neutralizing antibodies against both rotavirus and norovirus. The study, available online in Proceedings of the National Academy of Sciences, outlines an innovative approach to preventing one of the most common and intractable viral infections.
“Pretty much everyone has had norovirus at some point,” said senior author Siyuan Ding, PhD, an assistant professor of molecular microbiology. “You go out to eat, and the next thing you know you’re vomiting and having diarrhea. You will recover, but it’s going to be a rough three days or so. For kids in the developing world who don’t have access to clean water, though, it can be deadly. The rotavirus vaccines work really well, and there are already global distribution systems set up for them, so based on that, we saw an opportunity to finally make some headway against norovirus.”
Before the first rotavirus vaccines were rolled out in 2006, half a million children around the world died every year of diarrhea caused by rotavirus infection. Now, the number is estimated to be about 200,000 — still high but a huge improvement. Four rotavirus vaccines are in use around the world. All are live-virus vaccines, meaning they are based on weakened forms of rotavirus capable of triggering an immune response but not of making people sick.
Human norovirus, on the other hand, has stymied scientific investigation for decades. It doesn’t infect mice or rats or any other ordinary lab animals, so the kinds of experiments that led to the development of rotavirus vaccines have been impossible to replicate with norovirus.

Ding and colleagues — including first author Takahiro Kawagishi, PhD, a staff scientist in Ding’s lab, and co-corresponding author Harry B. Greenberg, MD, a professor emeritus of medicine at Stanford University — came up with the idea of using rotavirus to bypass the technical difficulties of working with norovirus. They worked with a laboratory strain of rotavirus as a stand-in for one of the approved rotavirus vaccines, which are proprietary.
The researchers inserted the gene for the protein that forms the outer surface of human norovirus into the genome of the rotavirus lab strain. Then, they administered the modified rotavirus to immunocompromised infant mice by mouth, the same way rotavirus vaccines are given to children. They took blood and fecal samples four, six and eight weeks later. Nine weeks after the initial immunization, the researchers gave the mice a booster by injection and took samples again a week later.
A strong antibody response was evident in the blood of nine of 11 mice tested, and in the intestines of all 11 mice. Even better, some of the antibodies from the blood and the intestines were able to neutralize both viruses in human “mini-gut” cultures in a dish. Such cultures, also known as organoids, are grown from human stem cells and replicate the surface of the human gut.
“Traditionally, vaccine studies have focused on the antibody response in the blood, because we understand that part of the immune response the best,” Ding said. “But norovirus and rotavirus are gut viruses, so antibodies in the blood are less important than the ones in the intestines in terms of fighting off these viruses. The fact that we saw a strong antibody response in the intestines is a good sign.”
The next step is to show that animals immunized with the experimental vaccine are less likely to get sick or die from norovirus. Ding has such experiments underway.
The power of this study is that it outlines a novel approach that could accelerate vaccine development for a variety of troublesome organisms that cause diarrhea, especially in resource-limited countries where many of these infections occur.
“There are a lot of intestinal pathogens out there for which we don’t have good treatments or vaccines,” Ding said. “In principle, we could put a gene from any organism that infects the intestinal tract into the rotavirus vaccine to create a bivalent vaccine. We’d have to find the right targets to produce a good immune response, of course, but the principle is simple.
“As basic scientists, we rarely get the chance to actually move something forward into the clinic,” Ding continued. “We study what the virus does and how the host responds at a basic level. This is a rare opportunity for our work to affect human health directly and make people’s lives better.”

Junior doctors sing their protest chants to popular tunes on picket lines in England.

Published15 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Dee familyBy Raffi BergBBC NewsFive people have received life-saving transplants from organs of a British-Israeli woman killed in a suspected Palestinian gun attack on Friday.The surgeries were carried out at two hospitals in Israel shortly before the funeral of Lucy Dee, 48, who died from her injuries on Monday.Two of her daughters were also killed in the attack as the family were driving in the occupied West Bank.The family moved to Israel from the UK nine years ago.Israel’s National Transplant Center said a 51-year-old woman received Lucy Dee’s heart; a 58-year-old woman one of her lungs; a 25-year-old man her liver; and a 58-year-old man and a 39-year-old man her kidneys. Her corneas have been preserved for future use.Lucy’s husband, Rabbi Leo Dee, told the Times of Israel that the family made the decision to donate her organs because “everything… that is lifesaving should be given”.Thousands of mourners attended Lucy Dee’s funeral in the West Bank Jewish settlement of Kfar Etzion, where two days earlier her two daughters – Rina, 15, and Maia, 20 – were buried in similar emotionally charged scenes. Government ministers attended both funerals.On Monday, Israeli Prime Minister Benjamin Netanyahu vowed to “get all the evil terrorists who killed our citizens and they will be held accountable with no exception”.Lucy, Rina and Maia were shot at as they were driving in the Jordan Valley on their way to a family holiday. Their vehicle crashed and the gunmen went up to the car and opened fire on the women at close range, Israeli media quoted investigators as saying.Israeli public broadcaster Kan reported that 22 bullet casings were found, apparently from a Kalashnikov assault rifle.The Israel Defense Forces (IDF) launched a hunt for the perpetrators following the attack, which came at a time of spiralling tensions between Israel and the Palestinians.On Monday, a 15-year-old Palestinian boy, Mohammad Balhan, was shot dead by Israeli troops in Aqabat Jabr refugee camp near Jericho in the West Bank, Palestinian officials said.The Israeli military said its forces were carrying out an operation to arrest militants in the camp at the time, and that they had returned fire after being shot at and attacked with explosives.Since the start of this year, more than 90 Palestinians – militants and civilians – have been killed by Israeli forces. Eighteen Israelis, a Ukrainian and an Italian – all civilians, except for an Israeli paramilitary police officer – have been also killed in attacks by (or suspected to have been carried out by) Palestinians and, in one case, an Israeli Arab.More on this storyUK-Israeli mother dies after West Bank shooting1 day agoFather mourns murdered daughters at West Bank funeral2 days agoBritish-Israeli sisters killed in West Bank named2 days agoRamadan and Passover raise tensions at Jerusalem holy site6 days agoTourist dead and 7 injured in Tel Aviv car-ramming3 days agoWhat is the crisis in Israel about?27 MarchIsraeli gun ownership rising as violence surges30 March

A new study’s finding that urban light pollution may disrupt the winter dormancy period for mosquitoes that transmit West Nile virus could be considered both good news and bad news.
The good news is that the disease-carrying pests may not survive the winter if their plans to fatten up are foiled. The bad news is their dormancy period, known as diapause, may simply be delayed — meaning they’re biting humans and animals longer into the fall.
“We see the highest levels of West Nile virus transmission in the late summer and early fall in Ohio. If you have mosquitoes postponing or delaying diapause and continuing to be active longer in the year, that’s at a time when the mosquitoes are most likely to be infected with West Nile virus and people could be at greatest risk of contracting it,” said Megan Meuti, senior author of the study and an assistant professor of entomology at The Ohio State University.
This study and earlier findings by Meuti and her colleagues are among the first to show that artificial light at night could have a significant impact on mosquito behavior — including effects that aren’t necessarily predictable.
“We’re finding that the same urban light at night can have very different effects under different seasonal contexts,” she said.
Meuti conducted the study with first author Matthew Wolkoff and Lydia Fyie, both PhD candidates in entomology at Ohio State. The research was published recently in the journal Insects.

Diapause for female Northern house mosquitoes (Culex pipiens) is not quite a winter slumber, but rather a period of dormancy when the insects live in caves, culverts, sheds and other semi-protected locations. Prior to winter’s arrival, mosquitoes convert sugary sources, such as plant nectar, into fat. As days get longer, females begin foraging for blood meals to enable egg production. Some get infected with West Nile virus by feeding on infected birds, and later transmit the virus when they feed on people, horses and other mammals.
This study builds upon two previous findings from Meuti’s lab: For her dissertation, Meuti found that circadian clock genes differ between diapausing and non-diapausing mosquitoes, strongly suggesting that day length dictates when diapause should start. And more recent work led by Fyie found that female mosquitoes exposed to dim light at night averted diapause and became reproductively active — even when short days indicated they should be dormant.
In the current study authored by Wolkoff, the researchers pursued both lines of inquiry, comparing daily activity and nutrient accumulation by mosquitoes reared in two lab conditions — long days mimicking the insects’ active season and short days that induced dormancy — with and without exposure to artificial light at night.
The study provided more evidence associated with a circadian pattern to mosquito behavior, showing that insects’ activity decreases during diapause, but the circadian rhythmicity of that activity is sustained even during this dormant period.
The introduction of artificial light at night was found to affect those activity patterns and to influence mosquitoes’ acquisition of nutrient reserves needed for fattening up and weathering winter temperatures.

Exposure to light pollution suppressed the amount of water-soluble carbohydrates — sugars that are an essential food source during winter — that were accumulated by mosquitoes in both long- and short-day conditions. Patterns of accumulation of the sugar glycogen were reversed by exposure to artificial light at night: Under normal conditions, non-dormant mosquitoes had lots of glycogen in their bodies but diapausing bugs did not — but in mosquitoes subjected to light pollution, the long-day mosquitoes didn’t accumulate much glycogen and short-day mosquitoes showed an increase in glycogen accumulation.
The researchers observed consistent trends in activity-related effects of light at night, with slight increased activity among the dormant mosquitoes and slightly suppressed activity among long-day mosquitoes expected to be busy looking for food. Though the findings weren’t statistically significant, Wolkoff said the combined observations suggest light pollution causes mosquitoes to ward off diapause — perhaps by scrambling signals from their circadian clock.
“This could be bad for mammals in the short term because mosquitoes are potentially biting us later in the season, but it could also be bad for mosquitoes in the long term because they might be failing to fully engage in preparatory activities they need to survive the winter during diapause, and that might reduce their survival rate,” Wolkoff said.
The researchers plan to carry out field studies to see if these lab findings hold true in the wild.
This work was funded by the National Science Foundation, state and federal funds appropriated to Ohio State’s College of Food, Agricultural and Environmental Sciences, and the U.S. Department of Agriculture National Institute of Food and Agriculture.

Babies tumble about with more than 200 previously unknown viral families within their intestines. This large number comes as a surprise to researchers from the University of Copenhagen and COPSAC, who closely studied the diapers of 647 Danish babies and made the first mapping of its kind. These viruses most likely play an important role in protecting children from chronic diseases.
Viruses are usually associated with illness. But our bodies are full of both bacteria and viruses that constantly proliferate and interact with each other in our gastrointestinal tract. While we have known for decades that gut bacteria in young children are vital to protect them from chronic diseases later on in life, our knowledge about the many viruses found there is minimal.
A few years back, this gave University of Copenhagen professor Dennis Sandris Nielsen the idea to delve more deeply into this question. As a result, a team of researchers from COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) and the Department of Food Science at UCPH, among others, spent five years studying and mapping the diaper contents of 647 healthy Danish one-year-olds.
“We found an exceptional number of unknown viruses in the faeces of these babies. Not just thousands of new virus species — but to our surprise, the viruses represented more than 200 families of yet to be described viruses. This means that, from early on in life, healthy children are tumbling about with an extreme diversity of gut viruses, which probably have a major impact on whether they develop various diseases later on in life,” says Professor Dennis Sandris Nielsen of the Department of Food Science, senior author of the research paper about the study, now published in Nature Microbiology.
The researchers found and mapped a total of 10,000 viral species in the children’s faeces — a number ten times larger than the number of bacterial species in the same children. These viral species are distributed across 248 different viral families, of which only 16 were previously known. The researchers named the remaining 232 unknown viral families after the children whose diapers made the study possible. As a result, new viral families include names like Sylvesterviridae, Rigmorviridae and Tristanviridae.
Bacterial viruses are our allies
“This is the first time that such a systematic an overview of gut viral diversity has been compiled. It provides an entirely new basis for discovering the importance of viruses for our microbiome and immune system development. Our hypothesis is that, because the immune system has not yet learned to separate the wheat from the chaff at the age of one, an extraordinarily high species richness of gut viruses emerges, and is likely needed to protect against chronic diseases like asthma and diabetes later on in life,” states Shiraz Shah, first author and a senior researcher at COPSAC.

Ninety percent of the viruses found by the researchers are bacterial viruses — known as bacteriophages. These viruses have bacteria as their hosts and do not attack the children’s own cells, meaning that they do not cause disease. The hypothesis is that bacteriophages primarily serve as allies:
“We work from the assumption that bacteriophages are largely responsible for shaping bacterial communities and their function in our intestinal system. Some bacteriophages can provide their host bacterium with properties that make it more competitive by integrating its own genome into the genome of the bacterium. When this occurs, a bacteriophage can then increase a bacterium’s ability to absorb e.g. various carbohydrates, thereby allowing the bacterium to metabolise more things,” explains Dennis Sandris Nielsen, who continues:
“It also seems like bacteriophages help keep the gut microbiome balanced by keeping individual bacterial populations in check, which ensures that there are not too many of a single bacterial species in the ecosystem. It’s a bit like lion and gazelle populations on the savannah.”
Shiraz Shah adds:
“Previously, the research community mostly focused on the role of bacteria in relation to health and disease. But viruses are the third leg of the stool and we need to learn more about them. Viruses, bacteria and the immune system most likely interact and affect each other in some type of balance. Any imbalance in this relationship most likely increases the risk of chronic disease.”
The remaining ten percent of viruses found in the children are eukaryotic — that is, they use human cells as hosts. These can be both friends and foes for us:

“It is thought-provoking that all children run around with 10-20 of these virus types that infect human cells. So, there is a constant viral infection taking place, which apparently doesn’t make them sick. We just know very little about what’s really at play. My guess is that they’re important for training our immune system to recognise infections later. But it may also be that they are a risk factor for diseases that we have yet to discover,” says Dennis Sandris Nielsen.
Could play an important role in inflammatory diseases
The researchers have yet to discover where the many viruses in the one-year-olds come from. Their best answer thus far is the environment:
“Our gut is sterile until we are born. During birth, we are exposed to bacteria from the mother and environment. It is likely that some of the first viruses come along with these initial bacteria, while many others are introduced later via dirty fingers, pets, dirt that kids put in their mouths and other things in the environment,” says Dennis Sandris Nielsen.
As Shiraz Shah points out, the entire field of research speaks to a huge global health problem:
“A lot of research suggests that the majority of chronic diseases that we’re familiar with — from arthritis to depression — have an inflammatory component. That is, the immune system is not working as it ought to — which might be because it wasn’t trained properly. So, if we learn more about the role that bacteria and viruses play in a well-trained immune system, it can hopefully lead us to being able to avoid many of the chronic diseases that afflict so many people today.”
The research groups have begun investigating the role of gut viruses in relation to a number of different diseases that occur in childhood, such as asthma and ADHD.
ABOUT BACTERIOPHAGES There are generally two types of bacteriophages. Virulent bacteriophages take over the bacterium and produce 30-100 new virus particles inside it. After this, the bacterial cell explodes from the inside and the new virus particles escape into the environment. Virulent bacteriophages help to keep the intestinal ecosystem in balance. So-called temperate bacteriophages can reproduce by integrating their genetic material into the genome of the host bacterial cell. When the cell divides, so does the bacteriophage. Temperate bacteriophages help transfer new genes to the bacteria so it becomes more competitive. However, there are also studies suggesting that an imbalance in the temperate bacteriophage population is associated with various diseases, e.g., inflammatory bowel disease.ABOUT VIRUSES A virus is a microorganism consisting of a genome — either DNA or RNA — encapsulated in a protein membrane. Viruses cannot multiply. Instead, a virus attacks a host cell, which it uses to make copies of itself. Viruses are classified into viral families, which are then divided into a larger number of viral genera and viral species. A more well-known example of a viral family is coronavirus, to which the viruses Covid-19, MERS, SARS and several common cold viruses belong.

Excessive alcohol consumption leads to painful hangovers and accompanying headaches, fatigue, and nausea. Drinking alcohol has also been linked to a raft of health problems in the human body, including heart disease, cirrhosis, and immune deficiency. One way to avoid those consequences would be to drink less, but researchers in China have introduced another way to mitigate hangovers and other adverse outcomes — a genetically-engineered probiotic.
In a paper published this week in Microbiology Spectrum, the researchers described their approach and reported that in experiments on mice, the treatment reduced alcohol absorption, prolonged alcohol tolerance, and shortened the animals’ recovery time after exposure to alcohol. The probiotic hasn’t yet been tested on humans, but the authors predicted that if it confers the same benefits, it could present a new way to reduce alcohol-induced health problems, and liver problems in general.
Meng Dong, Ph.D, at the Chinese Academy of Science’s Institute of Zoology, who worked on the study, noted that clinical applications may extend beyond alcohol-related conditions. “We believe that genetically engineered probiotics will provide new ideas for the treatment of liver diseases,” she said.
The human body primarily uses forms of an enzyme called alcohol dehydrogenase, or ADH, to metabolize alcohol. But some variants are more effective than others: Some studies have found that a form called ADH1B, found primarily in East Asian and Polynesian populations, is 100 times more active than other variants. Previous studies on mice have shown that viral vectors genetically engineered to express ADH1B can accelerate the breakdown of alcohol, but that approach hasn’t been shown to be safe in humans.
Motivated by those findings, Dong and her colleagues looked for a safer delivery method, focusing on the probiotic Lactococcus lactis, a bacterium often used in fermentation. They used molecular cloning to introduce the gene for human ADH1B into a bacterial plasmid, which was then introduced into a strain of L. lactis. Lab tests confirmed that the probiotic secreted the enzyme. The researchers encapsulated the probiotic to ensure it would survive against stomach acid, then tested it on 3 groups of 5 mice, each exposed to different levels of alcohol.
Untreated mice showed signs of drunkenness 20 minutes after exposure to alcohol. When the mice were placed on their backs, for example, they were unable to get back on their feet. But in the group that received a probiotic that expressed human ADH1B, half the mice were still able to turn themselves over an hour after alcohol exposure. A quarter never lost their ability to turn themselves over.
Further tests showed that 2 hours after exposure, blood alcohol levels in the control group continued to rise, while those in the probiotic-treated mice had begun to fall. In addition, the researchers found that treated mice showed lower levels of lipids and triglycerides in their livers, suggesting that the probiotic could alleviate alcohol-related damage to that organ.
The next step, Dong said, is to investigate whether the potential therapeutic effect of the modified probiotic extends to humans. “We are excited about the improvement of recombinant probiotics in acute alcohol-induced liver and intestinal damage,” Dong said.

Cell secretions like proteins, antibodies, and neurotransmitters play an essential role in immune response, metabolism, and communication between cells. Understanding cell secretions is key for developing disease treatments, but current methods are only able to report the quantity of secretions, without any detail as to when and where they are produced.
Now, researchers in the BIOnanophotonic Systems Laboratory (BIOS) in the School of Engineering and at the University of Geneva have developed a novel optical imaging approach that gives a four-dimensional view of cell secretions in both space and time. By placing individual cells into microscopic wells in a nanostructured gold-plated chip, and then inducing a phenomenon called plasmonic resonance on the chip’s surface, they are able to map secretions as they are being produced, while observing cell shape and movement.
As it provides an unprecedentedly detailed view of how cells function and communicate, the scientists believe their method, recently published in Nature Biomedical Engineering, has “tremendous” potential for pharmaceutical development as well as fundamental research.
“A key aspect of our work is that it allows us to screen cells individually in a high-throughput fashion. Collective measurements of the average response of many cells do not reflect their heterogeneity…and in biology, everything is heterogeneous, from immune responses to cancer cells. This is why cancer is so hard to treat,” says BIOS head Hatice Altug.
A million sensing elements
At the heart of the scientists’ method is a 1 cm2 nanoplasmonic chip composed of millions of tiny holes, and hundreds of chambers for individual cells. The chip is made of a nanostructured gold substrate covered with a thin polymer mesh. Each chamber is filled with a cell medium to keep the cells alive and healthy during imaging.

“Cell secretions are like the words of the cell: they spread out dynamically in time and space to connect with other cells. Our technology captures key heterogeneity in terms of where and how far these ‘words’ travel,” says BIOS PhD student and first author Saeid Ansaryan.
The nanoplasmonics part comes in thanks to a light beam, which causes the gold electrons to oscillate. The nanostructure is engineered so that only certain wavelengths can penetrate it. When something — like protein secretion — occurs on the chip’s surface to alter the light passing through, the spectrum shifts. A CMOS (Complementary Metal Oxide Semiconductor) image sensor and an LED translate this shift into intensity variations on the CMOS pixels.
“The beauty of our apparatus is that the nanoholes distributed across the entire surface transform every spot into a sensing element. This allows us to observe the spatial patterns of released proteins irrespective of cell position,” says Ansaryan.
The method has allowed the scientists to get a glimpse of two essential cellular processes — cell division and cell death — and to study delicate antibody-secreting human donor B-cells.
“We saw the cell content released during two forms of cell death, apoptosis and necroptosis. In the latter, the content is released in an asymmetric burst, resulting in an image signature or fingerprint. This has never before been shown at the single-cell level,” Altug says.
Screening for cell fitness
Because the method bathes the cells in a nutritious cell medium, and does not require the toxic fluorescent labels used by other imaging technologies, the cells under study can easily be recovered. This gives the method great potential for use in developing pharmaceutical drugs, vaccines, and other treatments; for example, to help researchers understand how cells respond to different therapies at the individual level.
“As the amount and pattern of secretions produced by a cell are a proxy for determining their overall effectiveness, we could also imagine immunotherapy applications where you screen patient immune cells to identify those that are most effective, and then create a colony of those cells,” says Ansaryan.

More than 400 executives said that the decision ignored both scientific and legal precedent and that, if the ruling stood, it would create uncertainty for the pharmaceutical and biotech industries.The pharmaceutical industry plunged into a legal showdown over the abortion pill mifepristone on Monday, issuing a scorching condemnation of a ruling by a federal judge that invalidated the Food and Drug Administration’s approval of the drug and calling for the decision to be reversed.The statement was signed by more than 400 leaders of some of the drug and biotech industry’s most prominent investment firms and companies, none of which make mifepristone, the first pill in the two-drug medication abortion regimen. It shows that the reach of this case stretches far beyond abortion. Unlike Roe v. Wade and other past landmark abortion lawsuits, this one could challenge the foundation of the regulatory system for all medicines in the United States.“If courts can overturn drug approvals without regard for science or evidence, or for the complexity required to fully vet the safety and efficacy of new drugs, any medicine is at risk for the same outcome as mifepristone,” said the statement.Also on Monday, the Justice Department filed a motion asking the U.S. Court of Appeals for the Fifth Circuit to stay the ruling by Judge Matthew J. Kacsmaryk of the U.S. District Court for the Northern District of Texas until the department’s appeal of the case could be heard. Judge Kacsmaryk, a Trump appointee who has written critically of Roe v. Wade, had issued only a seven-day stay of his ruling to allow the government a chance to appeal.“If allowed to take effect, the court’s order would thwart F.D.A.’s scientific judgment and severely harm women, particularly those for whom mifepristone is a medical or practical necessity,” said the Justice Department motion, which noted that mifepristone was also used in treating miscarriages. It added: “This harm would be felt throughout the country, given that mifepristone has lawful uses in every state. The order would undermine health care systems and the reliance interests of businesses and medical providers.”The appeals court gave the plaintiffs, a coalition of groups and doctors who oppose abortion, until midnight Tuesday to file a response.A lawyer for the plaintiffs, Erin Hawley, said in a statement on Monday, “Chemical abortion drugs don’t provide a therapeutic benefit — they can cause serious and life-threatening complications to the mother, in addition to ending a baby’s life.”She added that “the F.D.A. put women in harm’s way, and the agency should be held accountable for its reckless actions.”The Justice Department also filed a motion in a separate lawsuit over mifepristone. That case, filed in Washington State against the F.D.A. by 18 Democratic attorneys general who challenged extra restrictions that the agency imposes on the drug, produced a contradictory order less than an hour after the Texas ruling, which was issued on Friday evening.Judge Thomas O. Rice, an Obama appointee, did not lift the extra restrictions but told the F.D.A. not to do anything to limit current access to mifepristone in the jurisdictions that had filed the suit, which represent a majority of the states where abortion remains legal.In its motion in that case, the Justice Department said there was “significant tension” between the Texas and Washington rulings and asked Judge Rice to clarify what the F.D.A. would be obligated to do if the Texas ruling took effect — essentially seeking instructions from the judge that would allow the agency to continue to keep mifepristone available.The dueling rulings by two federal judges have set up a legal showdown that is likely to end up in the Supreme Court.”This is absolutely a test of our legal system’s ability to function,” Phil Weiser, the attorney general of Colorado, said in an interview. Colorado is a plaintiff in the Washington case and one of nearly two dozen states that signed briefs supporting the F.D.A. in the Texas case before both the district court and, on Monday, before the appellate court.Mr. Weiser said that the Texas decision violated “basic principles” about “how you make judgments based on evidence and about the authority of agencies.” He added, “The challenge is, once you start undermining those rules in one case, you undermine it for others as well.”The larger destabilizing potential of the Texas ruling was at the root of the letter signed by the biotech and pharmaceutical executives.Dr. Jeremy Levin, the chief executive of Ovid Therapeutics and the former chairman of BIO, a biotech trade association, said in an interview that he and a few other industry leaders had been worried about the Texas lawsuit since it was first filed in November. “It completely upends the F.D.A.’s authority,” Dr. Levin said of Judge Kacsmaryk’s ruling. “And then, much more importantly, it opens it up to a political determination of what a medicine is or isn’t, and that is deeply harmful for vaccines, Alzheimer’s drugs, all the others.” Dr. Shehnaaz Suliman, the chief executive of ReCode Therapeutics, said that she and Dr. Amanda Banks, the former chief executive of Blackfynn Therapeutics, began drafting the letter a few weeks ago, after a March 15 hearing in the case in Judge Kacsmaryk’s courtroom in Amarillo, Tex.“The primary message is the concern about the court’s overreach and how it might apply to other disease areas or products regulated by the F.D.A.,” said Dr. Suliman, who was involved in organizing a “call to action” among members of the industry in response to the Supreme Court’s decision last year to overturn Roe v. Wade.“The F.D.A.’s evaluation of safety and effectiveness for products is the gold standard in the world,” she said, “and our industry relies on this to foster the kind of innovation that has resulted in drugs that have saved millions.” On Friday evening, after the ruling was issued, Dr. Suliman and Dr. Banks shared their draft with Dr. Levin and three other executives, meeting with them virtually to fine-tune it. Then, Dr. Banks and others “pulled an all-nighter,” Dr. Levin said, working Friday night through Saturday to complete it.The group emailed the draft to about 100 leaders in the industry, many of whom signed and also circulated it to their employees and other industry executives, Dr. Levin said. Asked whether anyone declined to sign, he said, “In our experience, people don’t decline — they just don’t respond.”Most of the signatories are not involved in reproductive health. One signatory, Pfizer, makes a small percentage of the U.S. supply of the second drug in the medication abortion regimen, misoprostol, which is approved for other medical conditions but used off-label for abortion. A spokeswoman for Pfizer said that the company did not support off-label use of any of its medicines, but that the F.D.A. “serves a critical role in the U.S. public health system — bringing new medicines to patients and conducting ongoing safety reviews that support the continued use of them — that must be maintained.”Legal scholars said the Texas ruling appeared to be the first time a court had tried to invalidate the approval of a drug over the objection of the F.D.A. For decades, Congress has given the agency authority to determine whether drugs are safe and effective.The ruling could be so far-reaching for pharmaceutical companies that the letter from industry leaders is probably just the beginning of the industry’s actions to oppose it, said Jennifer Oliva, a professor of law at the University of California College of the Law, San Francisco, who signed a brief submitted to Judge Kacsmaryk’s court by drug policy scholars in support of the F.D.A.“They’re going to heavily lobby state legislatures, Congress and get involved in the courts in these battles going forward because it threatens their livelihood,” Ms. Oliva said.